tbuckley/cabot-search huggingface dataset:
Key factors associated with response in the treatment of liver metastatic melanoma by cryoablation combined with PD-1 blockade therapy: The Cryo-Fire-001 study.
Authors: Lujun Shen, Xiaoshi Zhang, Weijun Fan
Journal: Journal of Clinical Oncology (2023)

e21500 Background: Liver metastasis remains a challenge in the treatment of advanced stage melanoma through immunotherapy. Although our previous study showed cryoablation could enhance the efficacy of PD-1 blockade therapy in the treatment of melanoma patients with liver metastasis, the key factors correlated with survival and treatment response remains unknown. Methods: Between 2018 and 2022, 45 melanoma patients receiving combined PD-1 blockade therapy and cryoablation of liver metastasis were retrospectively analyzed. The technical parameters of cryoablation, the sequence of the combined treatment, tumor characteristics, important immune markers and their correlations with treatment response were evaluated. The associations between key factors and overall survival (OS) were determined by Cox regression. Results: Of the 45 patients, the 3-month overall response rate (RECIST 1.1 criteria) is 26.7%. Multivariate analysis showed the number of metastatic organs ( &gt; 2 vs ≤2; HR 3.54; 95% CI 1.32-9.49; P = 0.012), pretreatment LDH level ( &gt; 300 vs ≤300 U/L; HR 4.59; 95% CI 1.78-11.85; P = 0.002) and diameter of ablated lesion ( &gt; 30 vs ≤30 mm; HR 3.27; 95% CI 1.17-9.15; P= 0.024) were independent unfavorable prognostic factors for OS. Further analysis showed patients with larger intrahepatic tumors ablated had larger tumor size (P &lt; 0.001). A scatter plot by the two key variables showed patients with intrahepatic tumor size less than 45 mm and size of ablated lesion less than 30 mm had a marginally higher rate of 3-month response (10/28, 35.7%) compared to those not (2/17, 11.7%; P = 0.076). Large diameter of ablated lesion ( &gt; 30 mm) require more ablation needles and cause greater elevation in the level of IL-6, CD8+T cell to Treg cell ratio and neutrophil to lymphocyte ratio after cryoablation while these changes disappeared when tested one month later. Conclusions: Fine selection based on baseline characteristics of patients and size of intrahepatic lesion for cryoablation are essential to achieve a high response rate during cryoablation-PD-1 combination treatment for liver metastatic melanoma.
Machine learning models based on radiomics features to predict treatment response, biomarker status, and bone metastasis in patients with non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICIs).
Authors: Jisang Yu, Yury Velichko, Hyeonseon Kim, Nicolò Gennaro, Moataz Soliman, Leeseul Kim, Youjin Oh, Trie Arni Djunadi, Jeeyeon Lee, Liam Il-Young Chung, Sung Mi Yoon, Zunairah Shah, Won Jun Yang, Hye Sung Kim, Yunjoo Lee, Soowon Lee, Daeun Kang, Rishi Agrawal, Pascale Aouad, Young Kwang Chae
Journal: Journal of Clinical Oncology (2023)

e21217 Background: Radiomics can predict diagnosis, metastasis, actionable mutations and treatment response in NSCLC patients by analyzing the heterogeneity of tumors and its surrounding tissues from medical images. In this abstract, machine-learning models based on radiomic features, in patients with NSCLC, were established and evaluated. Methods: Patients with NSCLC and treated with ICIs were selected. Main tumor and peri-tumoral space were segmented on chest CT scans with contrast at the start of immunotherapy by four clinicians. Among 255 radiomic features were extracted using LIFEx software (IMIV/CEA, Orsay, France), the top 30 features with the highest Fleiss’ kappa coefficient were chosen. The Random Forest (RF) algorithm with mixed effects was utilized to develop models. We divided data into two groups as a training set (70%) and a validation set (30%) and conducted bootstrapping to evaluate the efficiency of the models. The performance of the models was determined by calculating the sensitivity, specificity, positive predictive values (PPV), and negative predictive values (NPV). Durable disease control, progression, clinical progression, EGFR mutations, bone metastasis was evaluated by each model. Durable disease control was defined as no progression of diseases for 24 weeks or more after initiation of ICIs according to RECIST 1.1. Progression was defined by RECIST 1.1 on the first follow-up CT. Clinical progression was defined when treatment was discontinued due to disease progression. Results: Total 102 patients were analyzed; 55 (53.9%) were female and 47 (46.1%) were male. The mean age at the start of ICI treatment was 65.6 [range: 22-89]. The multi-reader radiomics-based models predicts durable disease control, progression, clinical progression, EGFR mutation, and bone metastasis with a sensitivity of 0.700, 0.714, 0.286, 0.909, and 0.810, and specificity of 0.417, 0.444, 0.778, 0.200, and 0.222 respectively. The statistical values of the models are shown in the Table. Conclusions: The machine-learning models grounded on radiomics features has limited accuracy to prognosticate ICIs treatment outcome, EGFR mutations, and distant bone metastasis. Further studies with larger sample sizes are warranted. [Table: see text]
Efficacy and safety of polymeric micelle paclitaxel (pm-Pac) plus tislelizumab and carboplatin for first-line treatment of patients with advanced squamous non-small-cell lung cancer.
Authors: Meiqi Shi, Yufang Zhao, Li Wang, Wei Peng, Xiangzhi Zhu, Xingwang Li, Lv-hui Wang, An-mei Ma, Yi-qun Tang
Journal: Journal of Clinical Oncology (2023)

9036 Background: The pm-paclitaxel formulation for injection (pm-Pac), a novel drug delivery system composed of nanoparticle-encapsulated paclitaxel micelles, combined with cisplatin has been proven to improve clinical outcomes in patients with advanced non-small-cell lung cancer (NSCLC). But the efficacy and safety of pm-Pac in addition to PD-1/PD-L1 inhibitors had never been reported before. Methods: Treatment-naive, stage IIIB/IV Sq-NSCLC patients with ECOG PS 0-2(≤1, 91.1%) were eligible. Participants were given intravenous Tislelizumab (200mg, d1) plus pm-Pac (230 mg/m 2 , d1) and carboplatin (AUC 5, d1), every 3 weeks until progression or unacceptable toxicity, with local radiotherapy or surgery allowed if treatment needed. The primary endpoints were ORR and safety. The secondary endpoints include DCR, PFS, and OS. AEs were graded according to CTCAE v5.0. Results: From Nov 2021 to Dec 2022, 45 patients were enrolled. The median age was 68 years (range 41-84), and most were male (93%) and former/current smokers (87%). 3 patients had baseline brain metastases and 31 patients had baseline PD-L1 evaluated. Twenty-two patients (48.9%) received subsequent local treatment because of the stable efficacy, including 18 radiotherapy and 4 surgery. Among all, 2 achieved confirmed CR, 36 achieved PR, 7 achieved SD, ORR was 84.4% and DCR was 100%. PFS and OS were immature. Kaplan-Meier survival analysis indicated that the 6m-PFS rate was 94.8% (95%CI:89.8%，97.6%), and a total of 41 (91.1%) patients are still alive on 1L treatment at the last follow-up on Feb 2023.The most common TRAE were alopecia (91.1%), leukopenia (80%), peripheral neurosensory numbness (55.6%) and extremity pain (24.4%). The most common grade 3 or higher AE was neutropenia (33.3%), which is commonly associated with chemotherapy. Conclusions: This is the first report about the new chemo-drug pm-Pac plus PD-1 inhibitor regimen that significantly improved ORR for advanced Sq-NSCLC with a tolerable safety profile, supporting further development of this new combination in the first-line treatment. Response rates. [Table: see text]
Hematologic and transfusion outcomes in patients (pts) with lower-risk myelodysplastic syndromes (LR-MDS) receiving luspatercept: Real-world assessment in the community practice setting.
Authors: Sudipto Mukherjee, Cherrishe Brown-Bickerstaff, Angelica Falkenstein, Adeola Y. Makinde, Emily Bland, JaLyna Laney, Marné Garretson, Ali McBride
Journal: Journal of Clinical Oncology (2023)

7057 Background: Erythropoiesis-stimulating agents (ESAs) are used as first-line (1L) treatment (tx) for the management of symptomatic anemia in LR-MDS. Luspatercept is approved for pts with LR-MDS with ring sideroblasts (RS) who experience ESA failure and are transfusion dependent. We assessed clinical outcomes of pts with LR-MDS with RS, or MDS/myeloproliferative neoplasms with RS and thrombocytosis, treated with luspatercept in US community practices. Methods: This retrospective, observational cohort study used physician-abstracted chart data from community oncology clinics and included adults diagnosed with LR-MDS (including Very low- to Intermediate-risk IPSS-R status) on/after Jan 1, 2015 who received luspatercept for ≥ 3 months (mos) with ≥ 3 mos of follow-up. Transfusion burden (TB) was defined by number of sessions (ses) received in the 8 weeks (wks) prior to luspatercept tx (baseline) and the lowest number for any consecutive period ≥ 8 wks during wks 1–24 of tx: transfusion independent (TI); low TB (LTB), 1–3 ses; and moderate TB (MTB), 4–5 ses. Results: Of 253 pts, 219 (87%) had 1 tx prior to luspatercept tx and 31 (12%) received ≥ 2. ESAs were used as 1L tx in 210 pts (83%). Median follow-up was 5.7 mos. The most common reason for discontinuing initial MDS tx among patients who received ≥ 1 tx prior to luspatercept was lack of anemia improvement (133/250). At baseline, 21 (8%) pts were TI, 208 (82%) had LTB, and 24 (10%) MTB. Median duration of luspatercept tx was 10.8 mos. During wks 1–24, 20/21 (95%) pts remained TI and 201/232 (87%) pts with LTB/MTB at baseline achieved TI for ≥ 8 wks. The Table shows changes in median hemoglobin (Hb), absolute neutrophil count (ANC), and platelet (plt) count. Conclusions: Most pts with LR-MDS received 1L ESAs and over half discontinued the first tx prior to luspatercept due to lack of anemia improvement, highlighting the need for alternative options to improve clinical outcomes. Consistent with data from the MEDALIST trial, 87% of pts with LTB/MTB who received luspatercept achieved TI for ≥ 8 wks, supporting its clinical benefit in routine clinical practice. [Table: see text]
Analysis on real-world chemotherapy outcomes in patients (pts) with tyrosine kinase inhibitor (TKI) resistant advanced <i>EGFR</i>-mutant non–small-cell lung cancer (NSCLC) in the United States.
Authors: Dina Oksen, Emmanuelle Boutmy, Barbara Ellers-Lenz, Niki Karachaliou, Xiuning Le
Journal: Journal of Clinical Oncology (2023)

e21088 Background: Chemotherapy is the current standard of care for pts with EGFR-mutant NSCLC whose tumor develops EGFR TKI resistance. We are conducting a real-world study to understand resistance mechanisms to EGFR TKI and outcomes with subsequent therapies (targeted and non-targeted). Here we report outcome results for standard of care given after resistance to a first-line (1L) EGFR TKI. Methods: This is a non-interventional descriptive cohort study using electronic medical record data and biomarker data from the United States TEMPUS database, which will continue until end of 2024 with new pts entering the study cohort over time. The study period for this reported analysis on real-world chemotherapy outcomes was any time until June 2022. Drug resistance was defined as disease progression on an EGFR TKI. Pts entering the study cohort were adult, with stage IIIB–IV NSCLC, had received an EGFR TKI either as a monotherapy or in combination with other systemic therapies, and had disease progression after EGFR TKI initiation. Pts were followed after tumor progression and from the initiation of a chemotherapy regimen, to describe treatment patterns and treatment outcomes (real-world progression-free survival [rw-PFS] and overall survival [OS]). Results: Of 21,425 pts with NSCLC, 1,087 patients were eligible for inclusion into the study cohort, with their stage IIIB–IV NSCLC diagnosis spanning from 1999 to 2021. A total of 588 pts (54.1%) received a 1L EGFR TKI and a subsequent second-line (2L) systemic therapy after disease progression. Of these, 100 pts received 2L chemotherapy regimens (platinum-based chemotherapy, n = 48; taxane monotherapy, n = 12; taxane + other chemotherapy, n = 3; pemetrexed, n = 28; other chemotherapy-only regimens, n = 9). Overall, these chemotherapy-treated pts had a median rw-PFS of 4.3 months (95% CI: 3.3, 5.1), and a median OS of 14.2 months (95% CI: 11.8, 22.2). Conclusions: Here, we show that after disease progression on a 1L EGFR TKI, patients had poor disease outcomes on 2L chemotherapy, indicating an unmet medical need as these pts likely developed EGFR TKI resistance. Treatment adaptation based on identified mechanism of resistance such as MET amplification, may improve outcomes for these patients.
Improving guideline-concordant biomarker testing through implementation of a precision cancer medicine steward.
Authors: Rifeta Kajdic Hodzic, Elana Plotkin, Leigh Boehmer, Joseph Kim, Luis E. Raez, Crystal Enstad, Courtney Rice, Frank dela Rama
Journal: Journal of Clinical Oncology (2023)

e18706 Background: Gaps in guideline-concordant cancer biomarker testing exist in real-world clinical practice. Medically underserved populations, in particular, face significant challenges to accessing the latest advances in cancer diagnostics. As community cancer programs work to expand their approach to precision medicine, some have created a precision medicine “steward” who acts as a point person for removing barriers to biomarker testing. The Association of Community Cancer Centers (ACCC) explored the clinical utility, impact, and feasibility of having a precision medicine steward on the multidisciplinary cancer care team. Methods: ACCC held a series of focus groups and interviews with a diverse group of stakeholders to explore how cancer programs had justified, hired, trained, and utilized precision medicine stewards to improve guideline-concordant biomarker testing rates. ACCC examined select job descriptions, learned how stewards helped improve biomarker testing processes, and developed a framework for how a steward can fit into cancer care teams’ clinical and operational workflows. Results: Precision cancer medicine stewards can help improve biomarker test ordering processes. In one member program, turnaround time from test ordering to receipt of results decreased from an average of 24 days to 12 days and the quantity non-sufficient rate of testing decreased by five percent. Stewards also helped to improve the digitization of test orders, streamline prior authorizations, track tissue specimens, and notify oncologists when quantity of tissue was not adequate for testing. Stewards contributed to precision medicine workgroups that vetted reference laboratories, tracked key performance indicators around biomarker testing, and prioritized opportunities to reduce testing disparities. ACCC also collated examples of job titles, job descriptions, and role responsibilities of precision medicine stewards to share across member programs and practices. Conclusions: Guideline-concordant biomarker testing requires multiple complex steps and careful care coordination. Precision cancer medicine stewards have been shown to improve testing-related processes, decrease the time from ordering to receipt of results, and assist with prior authorizations. ACCC will work to further highlight their contributions on the multidisciplinary cancer care team and document more evidence of their return on investment for cancer programs and practices.
A biomarker study of atezolizumab (atezo) + bevacizumab (bev) + carboplatin (carbo) + paclitaxel (pac) (ABCP) for patients with NSCLC harboring <i>EGFR</i> mutations (EGFRm) after failure of TKI therapy: NEJ043.
Authors: Satoshi Watanabe, Naoki Furuya, Atsushi Nakamura, Jun Shiihara, Ichiro Nakachi, Hisashi Tanaka, Mika Nakao, Koichi Minato, Masahiro Seike, Shinichi Sasaki, Akira Kisohara, Susumu Takeuchi, Ryoichi Honda, Kei Takamura, Yiwei Ling, Shujiro Okuda, Hiroshi Kagamu, Kenichi Yoshimura, Toshiaki Kikuchi, Kunihiko Kobayashi
Journal: Journal of Clinical Oncology (2023)

9079 Background: EGFRm NSCLC patients (pts) have limited treatment options after EGFR-TKI failure. We previously showed that the NEJ043 study investigating ABCP in EGFRm NSCLC pts after EGFR-TKI failure had a clinically meaningful efficacy (Furuya et al, ASCO 2022). Here we report the results of the biomarker study of NEJ043. Methods: NEJ043 study is a phase II study to evaluate the efficacy of ABCP in sensitizing EGFRm nonsquamous NSCLC pts after TKI failure. Pts received atezo (1200 mg), bev (15 mg/kg), carbo (AUC 6 mg/mL/min), and pac (175 mg/m 2 ) every 3 weeks up to 4 cycles followed by atezo plus bev until loss of clinical benefit. Before treatment initiation and three cycles of ABCP, peripheral blood mononuclear cells (PBMCs) were collected, and immunophenotypic data at each time point was obtained by flow cytometry. Results: 60 pts were included in the NEJ043 study and PBMCs were obtained from 31 pts. Pts with a higher percentage of CD11b + DR low CD3 - CD14 + myeloid-derived suppressor cells (MDSCs) before ABCP had significantly longer PFS (median, 9.7 months (95% CI, 5.3-17.7) vs 5.6 months (95% CI, 3.9-8.1); HR 0.38; P = 0.0313). Further analysis of the immune cell phenotypes that changed between pre-treatment and the third course showed that pts with increased CD62L low CD8 + cells (median, 12.8 months (95% CI, 5.6-20.3) vs 5.7 months (95% CI, 4.4-8.1); HR 0.25; P = 0.003) and PD-1 + CCR7 - CD45RA - CD8 + cells (median, 8.5 months (95% CI, 5.6-13.8) vs 5.7 months (95% CI, 2.6-8.1); HR 0.37; P = 0.0324) had significantly longer PFS. Conclusions: Inhibition of MDSCs by ABCP, especially bev, may be important for EGFRm pts whose antitumor immunity is suppressed by MDSCs before treatment. Better PFS may be expected in pts in whom ABCP therapy induced CD62L low CD8 + effector T cells and PD-1 + CCR7 - CD45RA - CD8 + effector memory T cells. Clinical trial information: jRCTs031190066 .
Longitudinal follow-up and outcomes of pediatric and adult patients with SDH-deficient GIST.
Authors: Urania Dagalakis, Shadin Ghabra, Erika Kaschak, Maran Ilanchezhian, Jaydira Del Rivero, Markku Miettinen, Audra A Sutterwhite, B. J. Thomas, Donna Bernstein, Margarita Raygada, Crystal Flowers, Keith Killian, Paul S. Meltzer, Karlyne Reilly, Mary Frances Wedekind, Brigitte C. Widemann, Hari Sankaran, Andrew M. Blakely, John Glod
Journal: Journal of Clinical Oncology (2023)

11542 Background: Gastrointestinal stromal tumor (GIST) are gastrointestinal non-epithelial neoplasms most commonly driven by somatic mutations in KIT or PDGFRA. Approximately ten percent of GIST are due to germline mutations in SDHx or epigenetic loss of expression of SDHC. While KIT and PDGFRa driven GIST respond to treatment with tyrosine kinase inhibitors, effective systemic therapies for SDH-deficient GIST have not yet been identified. SDH-deficient GIST are indolent tumors that typically progress slowly over time. A better understanding of the natural history of patients with these neoplasms is critical to identify effective treatments and improve patient care. A cohort of patients with SDH-deficient GIST is followed at the NIH Clinical Center and through the NIH Pediatric and Wild-type GIST Clinic. The aim of this study is to characterize the long-term outcome of this cohort of patients. Methods: Data from patients with SDH-deficient GIST enrolled in a study Natural History and Biospecimen Acquisition for Children and Adults with Rare Solid Tumors (NCT03739827) from January 2019 through January 2023 at the NIH were evaluated. In addition to review of medical records and imaging, when available, tumors were characterized by sequencing of SDH genes. Germline analysis of SDH genes was offered to consenting patients and families. Results: Clinical information and specimens were collected from 77 GIST patients (median age at diagnosis 21.5, [range 7-57] years; 72.7% (56) female, 21.3% (21) male) were classified by molecular subtypes: 33.8% SDHC epimutation, 28.6% SDHA, 22.1% SDHB, 14.3% SDHC and 1.3% SDHD. Median age at presentation of SDHC epimutation was younger (14.5 years, range: 8-56) when compared to SDHA (27.5 years, range: 7-55), SDHB (22 years, range: 8-54), SDHC (18 years, range: 10-57) and SDHD (39 years, N = 1). Most commonly, patients had at least one surgery (55.8%) while a lower proportion had four or more (7.8%). Primary tumors occurred in the stomach with 26% having metastases at presentation the most common location being the liver (10.4%). Overall, 64.9% of patients were treated with imatinib, 39% were treated with sunitinib and 15.6% received other additional systemic therapies. Within the cohort there were 13% of patients with paragangliomas and 6.5% with chondromas while only 9.1% had a family history of GIST. Conclusions: Longitudinal follow-up of an SDH-deficient GIST patient cohort will allow for better understanding of the natural history including treatment history and survival of patients with this rare disease and will help to optimize strategies for treatment and follow-up of these patients.
Comparison of real-world mortality data among patients with glioblastoma (GBM) and metastatic pancreatic cancer (mPC) treated in the community oncology setting.
Authors: David Cosgrove, Kathleen Aguilar, Yunfei Wang, Charles Sykes, Sarah Reinwald, Emily Kubisiak, Zhaohui Su, Vasu Chandrasekaran, Larisa Stees, Rupa Iyer, Nicholas J. Robert
Journal: Journal of Clinical Oncology (2023)

e18805 Background: Evaluation of endpoints in oncology research requires accurate assessment of patients’ vital status. For real-world investigations of cancer populations, comprehensive capture of patients’ death dates may require several data sources. The intent of this evaluation was to assess capture of documented death dates across multiple datasets in the US community oncology setting. Methods: This was a retrospective observational study of adult patients with GBM or mPC who initiated treatment between 1 January 2019 and 31 December 2019 within The US Oncology Network. Patient demographic, clinical and treatment characteristics were sourced from an electronic health record (EHR) database, iKnowMed (iKM). Patients were followed until January 2023 with death dates captured from the iKM EHR (structured and unstructured fields), the iKM claims database, the Social Security Administration’s Death Master File, as well as a commercially available mortality dataset from Datavant comprised of obituary, claims and government records. Chart review was used to confirm if patients were alive on 15 January 2023. The overall capture rate of death information from each source was evaluated descriptively. Agreement was assessed using two approaches: 1) as death dates that were an exact match between sources and 2) as death dates that occurred within 30 days of each other and/or within the same month. Results: A total of 173 patients with GBM (median age 65 years, median follow-up time 12.0 months) and 990 patients with mPC (median age 68 years, median follow-up time 7.1 months) were included. Across all sources, 91.1% of the pooled population had at least one documented death date or were confirmed to be alive (85.5% and 92.1% of patients with GBM and mPC, respectively). Among patients with full day-month-year death dates from at least 2 sources (n = 835), 95.4% of death records were matched on the exact death dates. Among patients with any death record from at least 2 sources (n = 852), 99.3% of death records were matched within 30 days of each other or within the same month. Conclusions: The findings of this study describe the capture rate of mortality and vitality status in the US community oncology setting. Future analyses are planned to augment these assessments of concordance, sensitivity, specificity, positive predictive value and negative predictive value across the sources with comparison to death dates captured by the National Death Index. These insights are important for development of composite mortality databases, comprised of death information from multiple sources using appropriate tokenization and overlap methodologies.